Dynamic user equilibrium in public transport networks with passenger congestion and hyperpaths

This paper presents a dynamic user equilibrium for bus networks where recurrent overcrowding results in queues at stops. The route-choice model embedded in the dynamic assignment explicitly considers common lines and strategies with alternative routes. As such, the shortest hyperpath problem is extended to a dynamic scenario with capacity constraints where the diversion probabilities depend on the time at which the stop is reached and on the expected congestion level at that time. In order to reproduce congestion for all the lines sharing a stop, the Bottleneck Queue Model with time-varying exit capacity, introduced in Meschini et al. (2007), is extended. The above is applied to separate queues for each line in order to satisfy the First-In-First-Out principle within every attractive set, while allowing overtaking among passengers with different attractive sets but queuing single file. The application of the proposed model to a small example network clearly reproduces the formation and dispersion of passenger queues due to capacity constraints and thus motivates the implementation of the methodology on a real-size network case as the next step for future research

How Cell Geometry and Cellular Patterning Influence Tissue Stiffness

Cell growth in plants occurs due to relaxation of the cell wall in response to mechanical forces generated by turgor pressure. Growth can be anisotropic, with the principal direction of growth often correlating with the direction of lower stiffness of the cell wall. However, extensometer experiments on onion epidermal peels have shown that the tissue is stiffer in the principal direction of growth. Here, we used a combination of microextensometer experiments on epidermal onion peels and finite element method (FEM) modeling to investigate how cell geometry and cellular patterning affects mechanical measurements made at the tissue level. Simulations with isotropic cell-wall material parameters showed that the orientation of elongated cells influences tissue apparent stiffness, with the tissue appearing much softer in the transverse versus the longitudinal directions. Our simulations suggest that although extensometer experiments show that the onion tissue is stiffer when stretched in the longitudinal direction, the effect of cellular geometry means that the wall is in fact softer in this direction, matching the primary growth direction of the cells

Hyperthermic intraperitoneal chemotherapy in interval debulking surgery for advanced epithelial ovarian cancer: A single-center, real-life experience.

Background: An improvement in survival without increasing perioperative morbidity in patients with advanced epithelial ovarian cancer treated with hyperthermic intraperitoneal chemotherapy (HIPEC) after interval debulking surgery (IDS) has been recently demonstrated in a randomized controlled trial. This study was aimed at assessing the feasibility and perioperative outcomes of the use of HIPEC after IDS at a referral cancer center. Methods: Over the study period, 149 IDSs were performed. Patients who had at least International Federation of Gynecology and Obstetrics stage III disease, with <2.5 mm of residual disease (RD) at the end of surgery and were not participating in clinical trials received HIPEC. Moreover, specific exclusion criteria were considered. These patients were compared with 51 patients with similar clinical characteristics at the same institution and within the same timeframe who did not receive HIPEC. Results: No differences in patient or disease characteristics with the exception of the type of neoadjuvant chemotherapy (P =.002) were found between the 2 groups. As for surgical characteristics, significant differences were found in RD after IDS (P =.007) and in the duration of surgery (P <.001), whereas the bowel resection and diversion rates (P =.583 and P =.213, respectively) and the postoperative intensive care unit and hospital stays (P =.567 and P =.727, respectively) were comparable. The times to start adjuvant chemotherapy were also similar (P =.998). Equally, the rates of any grade of both intraoperative complications (P =.189) and early postoperative complications (P =.238) were superimposable. Conclusions: In the authors' experience, the addition of HIPEC to IDS is feasible in 35% for the population. This value might increase with changes in the inclusion/exclusion criteria. HIPEC does not increase perioperative complications and does not affect a patient's recovery or time to start adjuvant chemotherapy. HIPEC should be offered to select patients listed for IDS

HCC development is associated to peripheral insulin resistance in a mouse model of NASH

NAFLD is the most common liver disease worldwide but it is the potential evolution to NASH and eventually to hepatocellular carcinoma (HCC), even in the absence of cirrhosis, that makes NAFLD of such clinical importance. Aim: we aimed to create a mouse model reproducing the pathological spectrum of NAFLD and to investigate the role of possible co-factors in promoting HCC. Methods: mice were treated with a choline-deficient L-amino-acid-defined-diet (CDAA) or its control (CSAA diet) and subjected to a low-dose i.p. injection of CCl 4 or vehicle. Insulin resistance was measured by the euglycemic-hyperinsulinemic clamp method. Steatosis, fibrosis and HCC were evaluated by histological and molecular analysis. Results: CDAA-treated mice showed peripheral insulin resistance at 1 month. At 1-3 months, extensive steatosis and fibrosis were observed in CDAA and CDAA+CCl4 groups. At 6 months, equal increase in steatosis and fibrosis was observed between the two groups, together with the appearance of tumor. At 9 months of treatment, the 100% of CDAA+ CCl4 treated mice revealed tumor versus 40% of CDAA mice. Insulin-like Growth Factor-2 (IGF-2) and Osteopontin (SPP-1) were increased in CDAA mice versus CSAA. Furthermore, Immunostaining for p-AKT, p-c-Myc and Glypican-3 revealed increased positivity in the tumors. Conclusions: the CDAA model promotes the development of HCC from NAFLD-NASH in the presence of insulin resistance but in the absence of cirrhosis. Since this condition is increasingly recognized in humans, our study provides a model that may help understanding mechanisms of carcinogenesis in NAFLD. © 2014 De Minicis et al

HDL cholesterol protects from liver injury in mice with intestinal specific LXRα activation

Background and aims: Liver X receptors (LXRs) exert anti-inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects. Methods: Mice with intestinal constitutive LXRα activation (iVP16-LXRα) were exposed to intraperitoneal injection of carbon tetrachloride (CCl4) for 8 weeks, and in vitro cell models were used to evaluate the beneficial effect of high-density lipoproteins (HDL). Results: After CCl4 treatment, the iVP16-LXRα phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro-inflammatory genes. This anti-inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16-LXRα exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16-LXRα. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS-stimulated Kupffer cells, decreased TNFα-induced oxidative stress in hepatocytes and reduced NF-kB activity in both cells. SRB1 silencing reduced TNFα gene expression in LPS-stimulated KCs, and NOX-1 and IL-6 in HepG2. Conclusions: Intestinal activation of LXRα modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy

Effects of countdown displays in public transport route choice under severe overcrowding

The paper presents a route choice model for dynamic assignment in congested, i.e. overcrowded, transit networks where it is assumed that passengers are supported with real-time information on carrier arrivals at stops. If the stop layout is such that passenger congestion results in First-In-First-Out (FIFO) queues, a new formulation is devised for calculating waiting times, total travel times and route splits. Numerical results for a simple example network show the effect of information on route choice when heavy congestion is observed. While the provision of information does not lead to a remarkable decrease in total travel time, with the exception of some particular instances, it changes the travel behaviour of passengers that seem to be more averse to queuing at later stages of their journey and, thus, prefer to interchange at less congested stations